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Biomedical subjects

J Friedman

Publications and source records attributed to J Friedman.

At least 235 records · Page 13Linked to original sources
PubMed1980

Pharmacological disposition of N-(phosphonacetyl)-L-aspartate in humans.

The pharmacological disposition of N-(phosphonacetyl)-L-aspartate (PALA), an antitumor transition state analog currently in clinical trial, has been studied in 19 patients after i.v. administration of the agent at doses ranging from 800 to 5000 mg/sq m; PALA in biological specimens was assayed enzymatically, advantage being taken of its inhibition of L-aspartate carbamoyltransferase (EC 2.1.3.2) PALA disappeared from plasma biexponentially, with an average terminal t 1/2 of 5.3 hr. It was excreted in the urine unchanged; the 24-hr cumulative excretion was 85% of the administered dose. The average total clearance was 1.60 ml/kg/min and was linearly related to creatinine clearance, suggesting that in humans PALA is essentially cleared by glomerular filtration. The apparent volume of distribution of PALA was 309 ml/kg, approximately the sulfate space in humans. PALA penetrated into the central nervous system only to a limited extent. Tumor L-aspartate carbamoyltransferase activity was also measured before and 1.5 hr to 6 days after PALA administration; in all eight studies, a notable decrease in enzyme activity was observed.

Aspartate Carbamoyltransferase↗
PubMed1980

Penetration of N-(phosphonacetyl)-L-aspartate into human central nervous system and intracerebral tumor.

Cerebrospinal fluid (CSF) was obtained from five patients by lumbar puncture and from two patients by Ommaya reservoir tap after the i.v. administration of the antitumor agent N-(phosphonacetyl)-L-aspartate (PALA). PALA was quantified enzymatically by inhibition of the target enzyme, aspartate carbamoyltransferase. After a 1-hr infusion of PALA, its CSF concentration steadily rose until the eighth hr, at which time it was 12 to 40% of concurrent plasma concentration. PALA concentration then declined more gradually in CSF than in plasma, and CSF concentrations exceeded plasma concentrations by 24 hr. PALA concentration X time product in CSF was 12 to 25% of that in plasma. PALA was infused i.v. for 30 to 60 min into eight patients undergoing surgical resection if intracerebral tumors. Its concentration in intracerebral tumor was greater than or comparable to concentration in temporalis muscle in four of six patients from whom muscle was obtained. The PALA concentration in edematous brain tissue was consistently lower than the concentration in tumor or muscle. In a patient undergoing occipital lobectomy, the PALA concentration in brain was inversely proportional to the distance from the tumor. PALA reached concentrations in intracerebral tumor that appeared to be similar to concentrations reported previously in s.c. tumors, although biopsy techniques and conditions differed.

Aspartic Acid↗
PubMed1979

The effect of placebo and tricyclic antidepressants on cortical evoked potentials in depressed patients.

Cortical evoked potentials in depressives were recorded in order to study stimulus intensity control in this group, and also to study the effect of treatment. In a sample of 33 psychiatric patients, the amplitudes of visual and auditory evoked potentials were found to be significantly greater during depression, than at recovery. The changes which appeared to be due to recovery were found not only in patients treated with tricyclic antidepressants (n = 22), but in those who had recovered following treatment with placebo (n = 11). The changes were most evident in the auditory system. In addition, no diagnostic predictors differentiated depressed patients who subsequently recovered on placebo from those who did not. It is concluded that: (i) cortical evoked potentials may change in amplitude with emotional state; (ii) placebo may have physiological consequences usually attributed to drugs alone.

Adolescent↗
PubMed1979

Cortical evoked potentials and extraversion.

Stimulus intensity modulation was studied in extraverts and introverts. Auditory evoked potentials were recorded in 29 subjects and visual evoked potentials in 55. In both sensory modalities, extraverts showed considerably larger amplitudes of the late components of the evoked potentials, suggesting that they were more "open" to stimuli than introverts. In this way, extraverts' responses to simple stimuli could be seen as similar to their interchange with the complex stimuli of the social world.

Auditory Perception↗
PubMed1979

The menstrual cycle and habituation.

A group of women were studied over two consecutive menstrual cycles, at about one week intervals. Twenty-one of these women had spontaneous ovulatory menstrual cycles, 6 women had anovulatory cycles, and 7 were regular users of oral contraceptives. All cycles were converted to classic 28 day cycles. On each visit, a record was obtained of the subject's galvanic skin responses (GSRs) to 21 successive auditory stimuli. It was found that, during ovulatory cycles, a marked change in the rate of habituation of the GSR occurred around day 14 and day 28. During days 1--14 the mean habituation point (number of GSR responses to sound before 3 successive nonresponses) was 12.4 SE 1.6. This dropped to 6.8 SE 1.6 during days 15--28 (2-tailed t test, p less than 0.001). This change was not found for women on oral contraceptives, who showed consistent habituation rates throughout the cycle (mean habituation point 7.2 SE 1.1). The evidence also suggested that women with anovulatory cycles differed from those with ovulatory cycles in that they did not show a chnage in their habituation point around midcycle.

Acoustic Stimulation↗
PubMed1979

Enzymatic assay for the antitumor agent-N-(phosphonacetyl)-L-aspartic acid (PALA).

A method is described for the assay of N-(phosphonacetyl)-L-aspartic acid in plasma or urine, based on inhibition of partially purified aspartate carbamoyltransferase from rat liver. Concentrations of N-(phosphonacetyl)-L-aspartic acid as low as 0.1 microgram/ml can be detected. Plasma disappearance and urinary excretion curves from one patient are shown as examples of the application of the method.

Animals↗
PubMed1978

Pitfalls in the radiographic diagnosis of angiofibroma.

Radiographic findings previously thought pathognomonic for juvenile nasopharyngeal angiofibroma are anterior bowing of the posterior wall of the maxillary antrum on plain films or tomography, and a dense homogeneous blush on angiography. Two patients presented with nasopharyngeal masses which mimicked angiofibroma radiographically: one mass was a lymphoepithelioma and the other was a fibrous tumor. Constitutional symptoms and atypical physical findings should alert the physician to a diagnosis other than juvenile nasopharyngeal angiofibroma.

Adolescent↗
PubMed1978

The bruit of carotid stenosis versus radiated basal heart murmurs. Differentiation by phonoangiography.

Phonoangiography, quantitative analysis of arterial bruits, has been shown to provide accurate noninvasive diagnosis of uncomplicated carotid arterial stenosis, but had not been tested where cervical bruits from other sources were present. In this study, 27 carotid bruits in 15 consecutive patients with carotid bruits and basal heart murmurs were analyzed by phonoangiography. Tape recordings were made over the base of the heart and along the course of the carotid arteries in the neck; spectral analysis was performed as previously described. The spectral shape of the basal heart murmurs was recognizable and amplitude decreased with distance from the heart, althouth a secondary, lower amplitude, maximum often occurred over the carotid bifurcation. Intrinsic carotid bruits, by contrast, were always maximal over the bifurcation, and although they radiated both proximally and distally, were not detectable over the chest wall. In quantitative terms, the correct diagnosis as to the presence and extent of carotid stenosis was made in 25 of 27 cases (92%) despite the presence of a radiated murmur. Phonoangiography is capable of accurate differentiation of radiated murmurs from intrinsic carotid bruits and of quantitation of the latter even in the presence of radiated sounds.

Carotid Artery Diseases↗
PubMed1978

Comparison of spontaneous and contraceptive menstrual cycles on a visual discrimination task.

21 women with spontaneous ovulatory menstrual cycles, and 7 women who were regular users of oral contraceptives were investigated over two consecutive menstrual cycles. There two groups were compared on their two flash threshold performance and on mood ratings. It was found that, for women with ovulatory menstrual cycles, visual sensitivity was enhanced during the late follicular phase of the cycle, as ovulation approached. At other phases of the menstrual cycle (paramenstrual and luteal) visual sensitivity remained constant and comparable to the values found in women who were taking to the values found in women who were taking contraceptives. Women who were taking contraceptives showed no significant variation in visual sensitivity with phase of the menstrual cycle. The overall level of anxiety, as reflected by mood ratings was higher in women with spontaneous cycles compared to those taking contraceptives. Neither group, however, showed significant variation in anxiety with phase of the cycle.

Adolescent↗
PubMed1978

Failure to thrive associated with renal disease.

Failure to thrive is a clinical syndrome usually associated with severely reduced increments in height and weight. It is commonly present in patients with chronic renal failure and occurs occasionally in patients with recurrent urinary-tract infections or tubular disorders. Renal osteodystrophy, protein-calorie malnutrition, and chronic glucocorticoid administration have been shown to be important causes of growth failure in patients with renal disease. Altered hormone production, metabolism, or peripheral utilization and acidosis may be causally related to growth failure. Such factors as anemia and hypos-thenuria appear to play no direct role.

Acidosis↗
PubMed1977

Studies on the biological role of DNA methylation: III Role in excision of one-genome long single-stranded phi X 174 DNA.

Accumulation of replicative intermediates of the bacteriophage phi X174 was observed in E. coli C infected cells when phage DNA methylation has been inhibited by nicotinamide or when cells were infected with a temperature-sensitive mutant in gene A. Analysis of the accumulating replicative intermediates by electron microscopy revealed that these molecules are composed of double-stranded DNA rings with multiple-genome length single-stranded "tails". These results suggest that the single 5-methylcytosine residue present in the phage DNA serves as a recognition site for the gene A protein mediating the excision of one-genome long phage DNA. This excision process is oligatory for the final maturation of the phage.

Coliphages↗
PubMed1977

Salt conservation in familial dysautonomia (Riley-Day syndrome).

In some patients with familial dysautonimia, plasma renin activity shows a paradoxical response to postural stimuli, i.e., levels of plasma renin activity are high when the patient is in the supine position and fall significantly during subsequent ambulation. Furthermore, there is no coordinated release of plasma renin activity and aldosterone. The aim of the present study was to determine whether these findings are accompanied by a disturbance of salt conservation. Six patients were studied in a summer camp while on normal and low-salt diets. Plasma and urinary aldosterone levels rose sharply and appropriately when four of the patients were placed on a low-sodium diet. In these subjects, urinary sodium output fell sharply although three of them failed to attain sodium equilibrium by the third day of the low-sodium regimen. Elevation of early morning plasma renin activity appeared to correlate with an inversion in the normal day-night rhythm in urinary volume.

Adolescent↗
PubMed1976

Studies on the biological role of DNA methylation. II. Role of phiX174 DNA methylation in the process of viral progeny DNA synthesis.

In vivo inhibition of bacteriophage phiX174 DNA methylation by nicotinamide resulted in the accumulation of replicative intermediates with multiple-genome length single-stranded "tails". These abnormal replicative intermediates could not be chased into viral single-stranded circular DNA. The effect of nicotinamide on phage maturation and accumulation of abnormal replicative intermediates could be reversed by washing out the inhibitor. The results suggest that the single methyl group present in the viral DNA serves as a recognition site for a specific endonuclease, probably the gene A protein product, that is responsible for the excision of the single-stranded one-genome long viral DNA, before final maturation of the virus occurs.

Coliphages↗